免疫システム構築の情報伝達制御

• 研究課題/領域番号: 12051103
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 東京医科歯科大学
• 研究代表者: 烏山 一 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (60195013)
• 研究分担者: 徳久 剛史 千葉大学, 大学院・医学研究科, 教授 (20134364) ; 桂 義元 東京医科歯科大学, 大学院・医歯学総合研究科, 客員教授 (90027095)
• 研究期間 (年度): 2000 – 2002
• 研究課題ステータス: 完了 (2002年度)
• 配分額: 27,600千円 (直接経費: 27,600千円); 2002年度: 7,900千円 (直接経費: 7,900千円); 2001年度: 8,100千円 (直接経費: 8,100千円); 2000年度: 11,600千円 (直接経費: 11,600千円)
• キーワード: B細胞分化 / T細胞分化 / リンパ球前駆細胞 / 胚中心 / 遺伝子再構成 / プレB細胞レセプター / Btk / BLNK / サイトカイン / STAT / NK細胞 / CD94

研究概要

「リンパ球の初期分化を誘導・制御するシグナル伝達機構」「リンパ球の系列分岐・運命分岐を決定するシグナル伝達機構」「末梢リンパ組織における免疫系再構築のシグナル伝達機構」を研究課題とする3つの計画研究を設定して、8名の計画研究班員と15名の公募研究班員によって研究を遂行した。本調整班では、研究グループ間の連絡調整・情報交換、実験条件の統一のための共通試薬等の検定・購入等をおこない、効率よい研究推進のための支援体制強化につとめた。(1)ノックアウトマウスの作製に最適なgermline transmissionに優れたES細胞を樹立選別し、未分化状態に維持に必要な至適培養条件を見いだし、最良のES細胞の供給をおこなった。(2)DNAシークエンス決定支援をおこなった。(3)細胞培養に最適な牛胎児血清を選別し、培養条件の標準化、均一化をはかった。(4)ハイブリドーマなど共有細胞株の保存管理と供給をおこなった。(5)遺伝子改変動物の樹立と系統維持、供給をおこなった。このように研究支援体制を強化継続したことにより、免疫システム構築の情報伝達制御機構に関して多くの新知見をみいだし、その成果は国際雑誌に数多く発表することができた。さらに2003年2月20-23日に、3年間の研究の総括と成果発表・討論のため、海外の一流研究者を交えて、International Symposium on Regulation of Immune Response in Heath and Diseaseを開催した。

研究成果

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• [文献書誌] 烏山 一: "「B細胞の初期分化」標準免疫学第2版(谷口克、宮坂昌之編)"医学書院. 9 (2002)
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• [文献書誌] Zhang, H., et al.: "A novel functional domain of Bc16 family that recruits histone deacethylases"Biochim.Biophys.Acta. 1543. 188-200 (2001)
• [文献書誌] Bannai, M. et al.: "Abundance of unconventional CD8(+) natural killer T cells in the large intestine"Eur.J.Immunol.. 31. 3361-3369 (2001)
• [文献書誌] Mizushima, N., et al.: "Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells"J.Cell Biol.. 152. 657-668 (2001)
• [文献書誌] Hamada, H. et al.: "Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine"J.Immunol.. 168. 57-64 (2002)
• [文献書誌] Murasawa, M., et al.: "GL7 defines the cycling stage of pre-B cells in murine bone marrow"Eur.J.Immunol.. 32. 291-298 (2002)
• [文献書誌] Ikawa, T., et al.: "Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2"Proc.Natl.Acad.Sci.USA. 98. 5164-5169 (2001)
• [文献書誌] Ohmura, K., et al.: "Immature multipotent hematopoietic progenitors lacking long-term bone marrow-reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses"J.Immunol.. 166. 3290-3296 (2001)
• [文献書誌] Shimizu, C., et al.: "Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity"Int.Immunol.. 13. 105-117 (2001)
• [文献書誌] Egawa, T., et al.: "The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor"Immunity. 15. 1-20 (2001)
• [文献書誌] Yoshida, H., et al.: "Expression of a4b7 intergrn defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells"J.Immunol.. 167. 2511-2521 (2001)
• [文献書誌] Itoi, M., et al.: "Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage"Int.Immunol.. 13. 1203-1211 (2001)
• [文献書誌] Katsura, Y.: "Stepwise lineage restriction of progenitors in lympho-myelopoiesis"Int.Rev.Immunol.. 20. 1-20 (2001)
• [文献書誌] Katsura, Y., et al.: "Redefinition of lymphoid progenitors"Nature Rev.Immunol.. 2. 127-132 (2002)
• [文献書誌] Ueno, T., et al.: "Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus"Immunity. (in press). (2002)
• [文献書誌] Yoh, K., et al.: "Transgenic overexpression of MafK suppresses T cell proliferation and function in vivo"Genes to Cells. 6. 1055-1066 (2001)
• [文献書誌] Tada M., et al.: "Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells"Current Biology. 11. 1553-1558 (2001)
• [文献書誌] Sano, S., et al.: "Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival"Immunity. 15. 261-273 (2001)
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• [文献書誌] Toyama-Sorimachi, N., et al.: "Mouse CD94 participates in Qa-1-mediated self recognition by NK cells and delivers inhibitory signals independent of Ly-49"J.Immunol.. 166. 3771-3779 (2001)
• [文献書誌] Kouro, T., et al.: "Bruton's tyrosine kinase (Btk) is required for signaling the CD79b-mediated pro-B to pre-B cell transition"Int.Immunol.. 13. 485-493 (2001)
• [文献書誌] Agematsu, K., et al.: "Complete arrest from pro-to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations"Clin.Exp.Immunol.. 124. 461-464 (2001)
• [文献書誌] Kinoshita, T., et al.: "Oncostatin M suppresses generation of lymphoid progenitors in fetal liver by inhibiting the hepatic microenvironment"Exp.Hematol.. 299. 1091-1097 (2001)
• [文献書誌] Kubo, S., et al.: "Drastic up-regulation of high affinity IgE receptor on mast cells is induced by IgE binding through stabilization and accumulation of the receptor on the cell surface"J.Immunol.. 167. 3427-3434 (2001)
• [文献書誌] Stephan, R.P.: "Analysis of VpreB expression during B lineage differentiation in lambda5-deficient mice"J Immunol. 167. 3734-3739 (2001)
• [文献書誌] Wang, Y-H., et al.: "Differential surrogate light chain expression governs B cell differentiation"Blood. (in press). (2002)
• [文献書誌] Honda, K., et al.: "Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis"J.Exp.Med.. 193. 621-630 (2001)
• [文献書誌] Agata, Y., et al.: "Histone acetylation determines the developmentally regulated accessibility for T cell receptor-γ gene recombination"J.Exp.Med.. 193. 873-879 (2001)
• [文献書誌] Lee, H.-C., et al.: "Induction of germline transcription in the human T cell receptor γ locus by STAT5"J.Immunol. 167. 320-326 (2001)
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• [文献書誌] Sakamoto, M., et al.: "Maternal germline mosaicism of X-linked agammaglobulinemia"Am.J.Med.Genet.. 99. 234-237 (2001)
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• [文献書誌] Toyama-Sorimachi,N., et al.: "Mouse CD94 participates in Qa-1-mediated self recognition by NK cells and delivers inhibitory signals independent of Ly-49."J.Immunol.. (In press).